The discovery that the control system in the synthesis of steroid hormones in the adrenocortical carcinoma cell has undergone considerable modification in the action of the hormone, ACTH, has led to the proposal that the adrenal tumor cell may have a) a different type of cGMP control in steroidogenesis and b) a modified cAMP-activated protein kinase enzyme system and c) a different type of membrane effect, as compared to the normal isolated adrenal cell. In the planned research the mutant strains of the adrenal tumor tissue culture cells, which respond in different manners to the hormone, ACTH, will be used. Using cGMP-binding protein from lobster muscle, the levels of cGMP in response to ACTH will be measured. The study on the protein kinase enzyme will be made by established biochemical techniques and the investigation on the role of ACTH and cAMP in the control of membrane phosphorylation will be done by the application of (P32) and (P33) orthophosphates. Comparison of the mechanisms of control of steroid synthesis and membrane phosphorylation processes in both normal and adrenal tumor cells will be made. This should make possible a better understanding of the abnormal control phenomena which have occurred in the transformation of a normal adrenal to a tumor adrenal cell. BIBLIOGRAPHIC REFERENCES: Sharma, R.K.: Regulation of Steroidogenesis in Adrenocortical Carcinoma. In "Control Mechanisms in Cancer", ed. Criss, W.E., Ono, T., and Sabine, J.R., pp 109-124 (1976) Raven Press, N.Y. Sharma, R.K., Ahmed, N.K. and Shanker, G.: Metabolic Regulation of Steroidogenesis in Adrenocortical Carcinoma Cells of Rat. Relationship of Endogenous Protein Kinase Activity and Steroidogenesis. Cancer Res. 37, 472 (1977).